The pathogenesis of type 2 diabetes is believed to involve two core defects: insulin resistance and β-cell failure (Martin et al., Lancet, 340:925-929 (1992); Weyer et al., J. Clin. Invest., 104:787-794 (1999); DeFronzo et al., Diabetes Care, 15:318-368 (1992)). Important advances towards the understanding of the development of peripheral insulin resistance have been made in both animal models and humans (Bruning et al., Cell, 88:561-572 (1997); Lauro et al., Nat. Genet., 20:294-298 (1998); Nandi et al., Physiol. Rev., 84:623-647 (2004); Sreekumar et al., Diabetes, 51:1913-1920 (2002); McCarthy and Froguel, Am. J. Physiol. Endocrinol. Metab., 283:E217-E225 (2002); Mauvais-Jarvis and Kahn, Diabetes. Metab., 26:433-448 (2000); Petersen et al., N. Engl. J. Med., 350:664-671 (2004)). However, the mechanisms underlying β-cell failure in humans are less well understood, partly due to difficulty accessing the pancreas, and the small contribution of islets to the total pancreatic mass.